The abilities of malignant tumor cells to invade adjacent tissues and spread via the blood to implant, invade and form secondary metastases at distant host sites are determined by both tumor and host properties. Using selected animal and human metastatic models as well as clinical biopsy samples consisting of primary tumors and their metastases, we will continue ongoing work on identifying, isolating, characterizing and developing useful diagnostic assays for metastasis-associated cell surface glycoproteins, proteoglycans, enzymes and antigens. In addition, we will examine gene expression in metastatic and nonmetastatic cells and identify genes which are differentially expressed as well as study the relationship between oncogene insertion, expression and tumor diversification mechanisms. We will also examine certain host properties which may be important in blood-borne metastasis such as organ specific determinants on endothelial cells. Using our recent techniques for isolating organ microvascular endothelial cells, the interactions of various metastatic cells with endothelial cells should allow us to determine the role of specific endothelial components in these processes.